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Deletion 9q34.3 syndrome: genotype-phenotype correlations and an extended deletion in a patient with features of Opitz C trigonocephaly
  1. S A Yatsenko1,
  2. S W Cheung1,
  3. D A Scott1,3,
  4. M J M Nowaczyk4,
  5. M Tarnopolsky5,6,
  6. S Naidu7,8,
  7. G Bibat8,
  8. A Patel1,
  9. J G Leroy1,9,
  10. F Scaglia1,3,
  11. P Stankiewicz1,
  12. J R Lupski1,2,3
  1. 1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
  2. 2Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
  3. 3Texas Children’s Hospital, Houston, TX, USA
  4. 4Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  5. 5Department of Medicine, McMaster University, Hamilton, Ontario, Canada
  6. 6Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
  7. 7Johns Hopkins University, Baltimore, MD, USA
  8. 8Kennedy Krieger Institute, Baltimore, MD, USA
  9. 9Department of Medical Genetics, Ghent University Hospital, Ghent, Belgium
  1. Correspondence to:
 Dr James R Lupski
 Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Room 604B, Houston, TX 77030, USA;

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Submicroscopic deletion del(9)(q34.3) is a rare constitutional microdeletion syndrome involving the gene-rich subtelomeric region of the long arm of chromosome 9, with about 30 cases reported.1,2,3,4,5,6,7,8,9,10,11,12 Visible constitutional 9q34 deletions are extremely rare, with only a few cases described.2,10,12 The low prevalence of large terminal deletions at the 9q34 chromosome region in liveborns is thought to reflect lethality in early embryogenesis.13

At least 18 patients with 9q34.3 microdeletions detected by fluorescence in situ hybridisation (FISH) testing, in whom normal karyotypes were initially obtained, have been reported.1,5–7,11 Many patients carry a cryptic del(9)(q34.3) that may result in a clinically recognisable phenotype characterised by severe developmental delay, mental retardation, hypotonia, congenital heart defects (CHD), seizures, and prominent craniofacial features including microcephaly, arched eyebrows, hypertelorism, short nose with anteverted nostrils, open mouth, and a protruding tongue.6,7,11 Recently, based on clinical and molecular breakpoint analyses using FISH, microsatellites, and single nucleotide polymorphism (SNP) genotyping, two research groups have independently identified an ∼1.0 Mb shortest region of overlap (SRO) of 9q34.3 deletions.6,11 Although the clinical criteria and incidence of the 9q34.3 deletion are not yet well established, the increasing number of patients reported with del(9)(q34.3) is probably related to the widespread clinical application of telomere FISH. Hence, this microdeletion syndrome may be more common than previously thought.

We have identified a 9q34.3 deletion in each of five unrelated patients, including a patient with clinical features similar to Opitz trigonocephaly C syndrome (OTCS; MIM 211750). A monogenic cause and autosomal recessive mode of inheritance have been considered probable in OTCS, usually associated with a normal karyotype.14–19 In contrast, several reports on patients with multiple congenital anomalies resembling OTCS and chromosomal …

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  • This study was supported in part by grants from the National Institute of Child Health and Human Development (PO1 HD39420) and the Mental Retardation Research Center (HD24064).

  • Competing interests: none declared